The focus of my research is the molecular epidemiology of upper aerodigestive tract cancers; with a primary interest in the epigenetics of cancer, in particular DNA methylation, and its diagnostic and prognostic biomarker applications. My current research has concentrated on use of an array-based approach for the identification of DNA methylation markers for head and neck cancer. My career goal is to develop an externally funded research program and establish myself as an independent academic investigator in the field of molecular cancer epidemiology. To facilitate this progression, I am proposing the following translational research and career development plan through the NCI K22 Career Transition mechanism. Oral & pharyngeal cancer accounted for an estimated 39,400 new cancer diagnoses in 2011, with 7,900 people dying of the disease. The prognosis is relatively poor, with an overall 5-year survival around 60% that worsens with increasing stage at diagnosis. Oral & pharyngeal cancers have among the highest risk of 2nd primary cancer of all solid tumors, along with a very high rate of disease recurrence, which are a major reason for treatment failure. Additionally, oral & pharyngeal cancer patients frequently suffer from high morbidity, including disfigurement and impairment of basic functions, such as talking, swallowing, eating and breathing. Much recent cancer biomarker research has focused on epigenetic alterations, with particular attention paid to DNA methylation due to its relative stability and amenability to measurement. Currently, no proven screening techniques are in wide-spread use for oral & pharyngeal cancer aside from visual inspection and palpation. Use of oral rinse as a non-invasive technique for sample collection may have utility in detection of DNA methylation in oral & pharyngeal cancers and therefore has potential in biomarker-based clinical applications. Hence, this proposal seeks to apply an epigenome-wide array-based approach to oral rinse samples to identify novel DNA methylation markers of oral & pharyngeal cancer that can facilitate early diagnosis and predict disease outcome (including survival and risk of recurrence or development of a 2nd primary) using the existing population resources of a large case-control study of head and neck cancer. Further, to progress to research independence in the highly complex field of molecular cancer epidemiology, I will require additional training and experience conducting bioinformatic analyses and lab-based molecular techniques for epigenetic analysis, in particular design and conduct of pyrosequencing assays. I also need to gain key experience in the comprehensive management of an NIH funded research project in molecular cancer epidemiology. This K22 award will afford me the opportunity to obtain the necessary experience and further develop these areas through formal and informal training activities (including additional biostatistical coursework), which are crucial to my transition to he independent stage of my research career in molecular cancer epidemiology.